We propose to develop the lingual taste bud in the rat and mudpuppy (Necturus maculosus) as a model for studying again processes at the cellular level, i.e. to correlate structure and function in the taste bud and examine the changes which occur during the lifespan of a taste bud cell. The lifespan of cells in the rat taste bud is only about 1-2 weeks (and is presently unknown in the mudpuppy). We will establish the lifespan of taste bud cells in the mudpuppy, using tritiated thymidine injections to examine cell renewal. We will test whether there are important alterations in the structure of chemoreceptor cells and their synapses as well as alterations in the chemosensitivity to applied tastants over this interval. Furthermore, we will test whether the nerve supply to the taste buds exerts a specific neurotrophic influence over the renewal of taste bud cells. These tests will incorporate histological and ultrastructural observations, using light microscopy, transmission electron microscopy, and high voltage electron microscopy (HVEM). The project will also use autoradiographic analyses at the light and electron microscopic level (including HVEM) to study the renewal of taste bud cells after injecting animals with tritiated thymidine. To corrrelate structure with function, we will impale single cells in the rat fungiform papillae and in the mudpuppy lingual papillae with microelectrodes and apply chemosensory stimuli iontophoretically. We will also dissociate taste buds in an attempt to patch clamp isolated cells and measure the unit conductance changes ovoked by chemosensory stimulation. The study will contribute to our understanding of aging, particularly vis-a-vis alterations of taste in the elderly. In addition, the data may be important to familial dysautonomia, a disease affecting the autonomic nervous system but which is also associated with marked degradation of the sense of taste. Finally, the experiments bear upon the general problem of trophic interactions in the nervous system and how the nerve supply to a tissue influences its development and maintenance.